Myopathy In Rats Research Articles

Stem cell biotherapy: A new remedy for Trichinella spiralis-induced inflammatory myopathy.

Trichinella spiralis (T. spiralis)-induced myopathy is an inflammatory myopathy that is difficult to treat unless the parasite is combated in its early intestinal phase before it reaches the muscles. This study aimed to evaluate the effect of local mesenchymal stem cell (MSC) therapy on T. spiralis-induced inflammatory myopathy in rats. Rats were divided into four groups: Group 1 (non-infected non-treated group); Group 2 (infected non-treated group); Group 3 (infected albendazole (ABZ)-treated group); and Group 4 (infected MSC-treated group). Their muscle status was assessed physiologically with the righting reflex and electromyography (EMG), parasitologically with the total muscle larval count, histopathologically with hematoxylin and eosin and Mallory's trichrome stains, as well as immunohistochemically for myogenin as a marker of muscle regeneration. Additionally, serum muscle enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as muscle matrix metalloproteinases MMP1 and MMP9, were assayed. Finally, the immunological response was assessed by measuring the levels of the muscle inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), and interleukin-4 (IL-4). Our findings revealed that MSC therapy markedly improved muscle EMG and righting reflex, as well as the histopathological appearance of the muscles, reduced inflammatory cellular infiltrates, and increased myogenin immunostaining. It also reduced serum CK and LDH levels, as well as muscle INF-γ, TNF-α, IL-4, MMP1, and MMP9 levels. However, it had no effect on the total muscle larval count. Accordingly, due to its anti-inflammatory properties and muscle-regenerative effect, MSC therapy could be a promising new remedy for T. spiralis-induced myopathy.

Mesenchymal stem cells versus intermittent fasting on statin induced myopathy in rats: The possible involvement of autophagy

Mesenchymal stem cells versus intermittent fasting on statin induced myopathy in rats: The possible involvement of autophagy

Histological and Immunohistochemical Study on the Effect of the Combined Vitamin C and Metformin versus Metformin Alone in Treating Diabetic Myopathy in Rat

Histological and Immunohistochemical Study on the Effect of the Combined Vitamin C and Metformin versus Metformin Alone in Treating Diabetic Myopathy in Rat

The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation.

Propofol infusion syndrome characterized by rhabdomyolysis, metabolic acidosis, kidney, and heart failure has been reported in long-term propofol use for sedation. It has been reported that intracellular adenosine triphosphate (ATP) is reduced in rhabdomyolysis. The study aims to investigate the protective effect of ATP against possible skeletal muscle damage of propofol in albino Wistar male rats biochemically and histopathologically. PA-50 (n = 6) and PA-100 (n = 6) groups of animals was injected intraperitoneally to 4 mg/kg ATP. An equal volume (0.5 ml) of distilled water was administered intraperitoneally to the P-50, P-100, and HG groups. One hour after the administration of ATP and distilled water, 50 mg/kg propofol was injected intraperitoneally to the P-50 and PA-50 groups. This procedure was repeated once a day for 30 days. The dose of 100 mg/kg propofol was injected intraperitoneally to the P-100 and PA-100 groups. This procedure was performed three times with an interval of 1 days. Our experimental results showed that propofol increased serum CK, CK-MB, creatinine, BUN, TP I, ALT, AST levels, and muscle tissue MDA levels at 100 mg/kg compared to 50 mg/kg and decreased tGSH levels. At a dose of 100 mg/kg, propofol caused more severe histopathological damage compared to 50 mg/kg. It was found that ATP prevented propofol-induced muscle damage and organ dysfunction at a dose of 50 mg/kg at a higher level compared to 100 mg/kg. ATP may be useful in the treatment of propofol-induced rhabdomyolysis and multiple organ damage.

Carvedilol: A Promising Drug Combined With Lipid-lowering Medications for Patients With Hypertension and Heart Failure

Background: Statins frequently cause myopathy especially in combination with fibrates, and physical activity is considered a trigger for the muscle disorder. Elevated plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and aldolase, are the main indicators of the severity of myopathy. Carvedilol is commonly used with lipid-lowering drugs in the management of heart failure, hypertension and dyslipidemia. It is not yet clear whether carvedilol, an alpha and β blocker, and anti-oxidant, may influence the development of myopathy when combined with statins and fibrates in cardiac patients. Methods: In this animal experiment, a 10 days regimen containing oral atorvastatin and gemfibrozil at doses of 80 and 1000 mg/kg/day, respectively, was used to induce myopathy in rats. The animals were forced to swim in a pool on days 8, 9 and 10 into the study. Carvedilol (2.5 mg/kg/day) was added to atorvastatin and gemfibrozil during the 10-day study period, in addition to the exercise protocol given to the treatment groups only. The mean of swimming tolerance times and the serum levels of CK, LDH and aldolase were measured at the completion of the study. Results: Carvedilol did not significantly alter the swimming tolerance time or the plasma levels of CK, LDH and aldolase in the rats receiving ATV, GMF and carvedilol plus the exercise protocol, compared with those that did not receive carvedilol (P>0.05). Conclusion: Carvedilol may be used in combination with lipid-lowering drug in the management of patients with heart failure and hypertension, pending its safety approval by clinical studies in humans.

Alleviation of Simvastatin-Induced Myopathy in Rats by the Standardized Extract of Ginkgo Biloba (EGb761): Insights into the Mechanisms of Action

Statins are the most widely prescribed cholesterol-lowering drugs to reduce the risk of cardiovascular diseases. Statin-induced myopathy is the major side effect of this class of drugs. Here, we studied whether standardized leaf extracts of ginkgo biloba (EGb761) would improve simvastatin (SIM)-induced muscle changes. Sixty Wistar rats were allotted into six groups: control group, vehicle group receiving 0.5% carboxymethyl cellulose (CMC) for 30 days, SIM group receiving 80 mg/kg/day SIM in 0.5% CMC orally for 30 days, SIM withdrawal group treated with SIM for 16 days and sacrificed 14 days later, and EGb761-100 and EGb761-200 groups posttreated with either 100 or 200 mg/kg/day EGb761 orally. Muscle performance on the rotarod, serum creatine kinase (CK), coenzyme Q₁₀ (CoQ₁₀), serum and muscle nitrite, muscle malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities were estimated. Additionally, muscle samples were processed for histopathological evaluation. We found that SIM decreased muscle performance on the rotarod, serum CoQ₁₀, as well as muscle SOD and CAT activities while it increased serum CK, serum and muscle nitrite, as well as muscle MDA levels. SIM also induced sarcoplasmic vacuolation, splitting of myofibers, disorganization of sarcomeres, and disintegration of myofilaments. In contrast, posttreatment with EGb761 increased muscle performance, serum CoQ₁₀, as well as muscle SOD and CAT activities while it reduced serum CK as well as serum and muscle nitrite levels in a dose-dependent manner. Additionally, EGb761 reversed SIM-induced histopathological changes with better results obtained by its higher dose. Interestingly, SIM withdrawal increased muscle performance on the rotarod, reduce serum CK and CoQ₁₀, and reduced serum and muscle nitrite while it reversed SIM-induced histopathological changes. However, SIM withdrawal was not effective enough to restore their normal values. Additionally, SIM withdrawal did not improve SIM-induce muscle MDA, SOD, or CAT activities during the period studied. Our results suggest that EGb761 posttreatment reversed SIM-induces muscle changes possibly through its antioxidant effects, elevation of CoQ₁₀ levels, and antagonizing mitochondrial damage.

Effect of Vitamin D Analogue on Rosuvastatin-Induced Myopathy in Wistar Rats.

Objectives Statin-induced myopathy is one of the major causes of poor adherence and discontinuation of this medication. There are contrary results regarding association of vitamin D insufficiency with statin-induced myopathy. This study was done to determine the effect of the vitamin D3 analogue alfacalcidol on Rosuvastatin-induced myopathy in rats. Methodology. Animals were divided into six groups with 6 rats in each group. Groups I and II acted as controls, Group III and Group IV were administered Rosuvastatin 120 mg/kg/day and 160 mg/kg/day, Groups V and VI were administered alfacalcidol 0.1 μg/kg/day in addition to Rosuvastatin 120 mg/kg/day and 160 mg/kg/day, respectively. All drugs were administered orally for 15 days. Plasma creatine kinase (CK) levels were estimated on day 10 and day 15. Animals were sacrificed and muscles were sent for histopathological examination. Results On day 10, Groups V and VI showed a statistically significant increase in plasma CK levels as compared to the control (p < 0.001) and were significantly lower (p < 0.001) as compared to Groups III and IV, respectively. However, on day 15, plasma CK levels in Groups V and VI were comparable to those of control groups with a nonsignificant difference (p > 0.05). On comparing the histology, Groups V and VI showed a significant difference as compared to statin-only groups (Groups III and IV) as there were signs of regeneration, less splitting, and fragmentation of muscle fibres. Conclusion The present study shows that the vitamin D analogue alfacalcidol prevents statin-induced myopathy. The serum CK levels are comparable to the control group on day 15 of vitamin D administration.

Effect of L-carnitine on the skeletal muscle contractility in simvastatin-induced myopathy in rats.

Abstract Background Statins therapy is effective in the prevention of cardiovascular events. However, its use is associated with skeletal muscle myopathy, which may be severe enough to discontinue statin therapy, thus exposing patients to more morbidity and mortality. This study was conducted to assess the effect of L-carnitine on the skeletal muscle contractility in a rat model of statin-induced myopathy and to clarify its possible mechanisms. Methods Twenty-one female Sprague Dawley rats were used throughout this study. The rats were divided into the normal control group, statin-induced myopathy group and statin/L-carnitine-treated group. The assessment of gastrocnemius muscle contractility, plasma creatine kinase (CK) levels and oxidative stress markers (malondialdehyde, reduced glutathione) was also carried out done. Results The results of the current study suggest that simvastatin decreased the skeletal muscle mass and altered the muscle contractile properties. It also significantly increased plasma CK level and induced a state of oxidative stress state (high MDA, low GSH). Meanwhile, concurrent L-carnitine significantly reduced statin-induced myopathy and improved the oxidative stress markers and skeletal muscle contractile parameters. Conclusions Statin myopathy is postulated to be due to mitochondrial dysfunction, cellular oxidative stress, induction of apoptosis, reduction in the expression of chloride channel and its related conductance, in addition to the alteration of Ca2+ homeostasis. L-carnitine has an antioxidant effect, reduces skeletal muscle atrophy and improves the skeletal muscle contractility in simvastatin-induced myopathy.

Thymoquinone Attenuates Cardiomyopathy in Streptozotocin-Treated Diabetic Rats.

Diabetic cardiomyopathy is a diabetic complication due to oxidative stress injuries. This study examined the protecting influence of thymoquinone (TQ) on diabetes-caused cardiac complications. The intracellular means by which TQ works against diabetes-caused cardiac myopathy in rats is not completely understood. In this study, Wistar male rats (n = 60) were assigned into four groups: control, diabetic (diabetes induced by IP infusion of streptozotocin, 65 mg/kg), diabetic + TQ (diabetic rats given TQ (50 mg/kg) administered once per day by stomach gavage), and TQ (50 mg/kg) for 12 weeks. TQ supplementation appreciably recovered the cardiac parameters alongside significant declines in plasma nitric oxide concentrations and total superoxide dismutase (T.SOD) activities. Importantly, TQ downgraded expression of cardiac-inducible nitric oxide synthase in addition to significantly upregulating vascular endothelial growth factor and erythropoietin genes and nuclear factor-erythroid-2-related factor 2 (Nrf2) protein. TQ normalized plasma triacylglycerol and low-density lipoprotein-cholesterol and significantly improved the high-density lipoprotein-cholesterol levels. Additionally, TQ administration improved the antioxidant ability of cardiac tissue via significantly increased cardiac T.SOD and decreased cardiac malondialdehyde levels. Oral supplementation with TQ prevented diabetic-induced cardiomyopathy via its inhibitory effect on the E-selectin level, C-reactive protein, and interleukin-6. The TQ protecting effect on the heart tissue was shown by normalization of the plasma cardiac markers troponin I and creatine kinase. This experiment shows the aptitude of TQ to protect cardiac muscles against diabetic oxidative stress, mainly through upregulation of Nrf2, which defeated oxidative damage by improvement of the antioxidant power of cardiac muscle that consequently protected the cardiac muscles and alleviated the inflammatory process.

Histomorphologic and ultrastructural recovery of myopathy in rats treated with low-level laser therapy.

The purpose of the present work was to study the effect of low-level laser therapy (LLLT): helium-neon (He-Ne) and gallium arsenide (Ga-As) laser on the histomorphology of muscle and mitochondria in experimental myopathy in rats. Thirty Suquía strain female rats were distributed in groups: (A) control (intact), (B) injured, (C) injured and treated with He-Ne laser, (D) injured and treated with Ga-As laser, (E) irradiated with He-Ne laser on the non-injured muscle, and (F) irradiated with Ga-As laser on the non-injured muscle. Myopathy was induced by injecting 0.05mg/rat/day of adrenaline in the left gastrocnemius muscle at the same point on five consecutive days, in groups B, C, and D. LLLT was applied with 9.5Jcm-2 daily for seven consecutive days in groups C, D, E, and F. The muscles were examined with optic and electronic microscopy. The inflammation was classified as absent, mild, and intense and the degree of mitochondrial alteration was graded I, II, III, and IV. Categorical data were statistically analyzed by Chi-square and the Fisher-Irwin Bilateral test, setting significant difference at p < 0.05. The damage found in muscle and mitochondria histomorphology in animals with induced myopathy (B) was intense or severe inflammation with grade III or IV of mitochondrial alteration. They underwent significant regression (p < 0.001) compared with the groups treated with He-Ne (C) and Ga-As (D) laser, in which mild or moderate inflammation was seen and mitochondrial alteration grades I and II, recovering normal myofibrillar architecture. No differences were found between the effects caused by the two lasers, or between groups A, E, and F. Group A was found to be different from B, C, and D (p < 0.001). LLLT in experimental myopathy caused significant muscular and mitochondrial morphologic recovery.

Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model.

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology.

Effect of the route of stem cell transplantation on its therapeutic potential on induced myopathy in rats

BackgroundMyopathies are diseases of skeletal muscle, in which there is a primary functional or structural impairment. No standard therapeutic guidelines exist. The use of stem cells may provide dramatic advances in their treatment.AimThe aim of this study was to evaluate the potential therapeutic e

Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid-treated rats.

Glucocorticoids cause secondary osteoporosis and myopathy, characterized by type II muscle fiber atrophy. We examined whether a new vitamin D3 analogue, eldecalcitol, could inhibit glucocorticoid-induced osteopenia or myopathy in rats, and also determined the effects of prednisolone (PSL) and/or eldecalcitol on muscle-related gene expression. Six-month-old female Wistar rats were randomized into four groups: PSL group (10mg/kg PSL); E group (0.05µg/kg eldecalcitol); PSL+E group; and control group. PSL, eldecalcitol, and vehicles were administered daily for 2 or 4weeks. Right calf muscle strength, muscle fatigue, cross-sectional areas (CSAs) of left tibialis anterior muscle fibers, and bone mineral density (BMD) were measured following administration. Pax7, MyoD, and myogenin mRNA levels in gastrocnemius muscles were also determined. Muscle strength was significantly higher in the PSL+E group than in the PSL group (p<0.05) after 4weeks, but not after 2weeks. No significant difference in muscle fatigue was seen between groups at 2 or 4weeks. CSAs of type II muscle fibers were significantly larger in the E group and the PSL+E group than in the PSL group at 4weeks (p=0.0093, p=0.0443, respectively). Eldecalcitol treatment for 4weeks maintained the same BMD as the PSL+E group. After 2weeks, but not 4weeks, eldecalcitol treatment significantly increased Pax7 and myogenin mRNA expression in gastrocnemius muscle, and PSL also stimulated myogenin expression. Eldecalcitol appears to increase muscle volume and to protect against femur BMD loss in PSL-administered rats, and it may also stimulate myoblast differentiation into early myotubes.

Abstract 13907: Statin-Induced Myopathy is Mediated by Isoprenoid Depletion and is Independent of Serum Cholesterol Levels

Statin use is associated with muscle-related side-effects (ie, MRSE) in ~10-20% patients and is the most common reason for discontinuation of treatment. Moreover, high-risk patients who have inadequately controlled LDL-C as a result of statin intolerance present a significant public health problem. A study to assess the role of cholesterol and/or isoprenoid intermediates of the cholesterol biosynthetic pathway in statin-induced myopathy was conducted in female rats treated with cerivastatin for 14 days. Cerivastatin treatment of rats fed standard diet induced myopathy in type II muscle fibers, but not in type I muscle fibers. Cholesterol supplementation in the diet of cerivastatin treated rats increased circulating cholesterol levels, but failed to prevent myopathy, suggesting that statin-mediated myopathy was independent of the cholesterol lowering effects of statins. Conversely, mevalonate supplementation of the diet abrogated cerivastatin induced myopathy evidenced by either microscopy or sensitive biomarkers of muscle injury including AST, CK, sTnI, FABP3, and urinary myoglobin. These data suggest that statin-induced myopathy involves a cholesterol biosynthetic intermediate upstream of cholesterol and downstream of mevalonate. Most animals with myopathy had increased expression of genes involved in stress (UCP1, NRF2), inflammation (Alox5ap), and autophagy/mitophagy (GABARAP), and decreases in genes involved in energy production (GATM, ATP5b, ATP5f1) or mitochondrial biogenesis (PGC-1α). These data suggest that sensitive muscle fibers may have deficits in mitochondrial biogenesis in the presence of increased autophagy/mitophagy that result in an energy crisis. In addition, many of these genes have also been reported to be changed in human statin myopathy, suggesting a similarity in mechanisms between rats and humans. In conclusion, cerivastatin-induced myopathy in rats involves a step upstream of cholesterol in isoprenoid intermediary metabolism that likely results in an energy crisis. These data suggest that lowering of cholesterol by mechanisms other than HMG CoA inhibition-associated isoprenoid intermediate depletion would not be expected to result in myopathy.

The Study on The Mechanism of Cardiac Function Improvement of Dilated Myopathy in Rats By Transplantation of Bone Marrow Stroma Stem Cell

Bone marrow stroma stem cells(BMSSCs) have shown promising future in repairing injured myocardium.However,few studies have explored the potential mechanism of BMSSCs transplantation for dilated cardiomyopathy(DCM).In this study we aimed to examine whether BMSSCs transplantation can improves the cardiac function of dilated cardiomyopathy of rats and investigate the possible mechanism of BMSSCs transplantation improving the cardiac function of dilated cardiomyopathy according to investigate the collagen fiber deposition,capillary density,VEGF and its receptor expression.Global heart failure in Wistar rats was induced by means of adriamycin administration,after labeled with DAPI,BMSSCs were transplanted into the myocardium of rats which were divided into transplantation group and control group.At 1w,2w,3w,4w after transplantation,heart function was measured by hemodynamic,the deposition of collagen fiber,expressions of VEGF and its receptor and capillary density were checked by immunochemistry and RT-PCR.Immunofluorescence microscopy revealed that the transplanted BMSSCs were visible at four weeks after transplantation.Compared with the control group,the transplantation group had a significantly higher maximum rate of rise and decline(±dp/dt) of left ventricular pressure and left ventricular systolic pressure(P 0.05),as well as a significantly lower rate of left ventricular diastolic pressure(P 0.05).The deposition of collagen fibers in the myocardium of transplantation group was reduced,according to A value in transplant group is less than control group(P 0.05).The expression of VEGF and its receptor were significantly higher than those of control group,and the upregulation of VEGF and its receptors was unsynchronized,the capillary density is higher in transplantation group than control group after four weeks.Taken together,our results suggest that BMSSCs transplantation can improve dilated cardiomyopathy's heart function of rats,we found that BMSSCs transplantation prevented the fusion of collagen fibers to some extent,decrease the deposition of collagen fiber and maintained the orderly structural arrangement of myocardial tissue.BMSSCs transplantation can also promote the angiogenesis,in our study we found that capillary density increased,BMSSCs transplantation not only upregulated the expression of VEGF,but also upregulated the expression of VEGF receptors.Unsynchronized upregulation of VEGF and its receptors was observed which may promote angiogenesis continuously and steadily.

Can human cord blood-derived stem cells improve statin-induced myopathy in rats? A histological and immunohistochemical study

Background and aim of work Primary myopathies of skeletal muscle are diseases with worldwide prevalence for which effective treatment is urgently needed. The aim of this study was to investigate the ability of human umbilical cord blood (HUCB) stem cells to repair damaged skeletal muscle in a rat model of statin-induced myopathy. Materials and methods This study included 24 adult male albino rats divided equally into four groups: the control group; the myopathy group in which myopathy was induced by administration of simvastatin (80▒mg/kg/day orally for 6 weeks); the stem cell-treated myopathy group in which myopathy was induced by administration of simvastatin with subsequent local injection of 1×106 HUCB stem cells in the right gastrocnemius; and the untreated myopathy group in which myopathy was induced by administration of simvastatin and then left without treatment for 2 weeks. Specimens of the right gastrocnemius from all rats were prepared, sectioned, and subjected to H&E, Prussian blue, and Masson’s trichrome stains in addition to immunohistochemical staining for α smooth muscle actin to reveal myofibroblasts. The area% of collagen and muscle fibers and the number of myofibroblasts/high-power field were ascertained. All measurements were statistically analyzed. Results The gastrocnemius of the myopathy group showed frequent necrotic and damaged muscle fibers, which were replaced by fibrous and fatty tissues. Compared with control rats, there was significant decrease in the area% of muscle fibers and significant increase in the area% of collagen and in the number of myofibroblasts. Two weeks later, there was partial repair of the muscle with no significant differences between stem cell-treated and untreated myopathy groups, which reflects the failure of stem cells to repair damaged myofibers. Conclusion HUCB stem cells have poor therapeutic effect for myopathy and might be hindered by the complex environment of a severely inflamed and degenerated muscle.

Evaluation of inflammatory biomarkers associated with oxidative stress and histological assessment of magnetic therapy on experimental myopathy in rats

The effect of pulsed electromagnetic field (PEMF) therapy, also called magnetic therapy, upon inflammatory biomarkers associated with oxidative stress plasma fibrinogen, nitric oxide (NO), L-citrulline, carbonyl groups, and superoxide dismutase (SOD) was evaluated through histological assessment, in rats with experimental myopathy.The groups studied were: (A) control (intact rats that received PEMF sham exposures); (B) rats with myopathy and sacrificed 24 h later; (C) rats with myopathy; (D) rats with myopathy and treated with PEMF; and (E) intact rats treated with PEMF. Groups A, C, D, and E were sacrificed 8 days later. Myopathy was induced by injecting 50 μl of 1% carrageenan λ (type IV) once sub-plantar. Treatment was carried out with PEMF emitting equipment with two flat solenoid disks for 8 consecutive days in groups D and E, at 20 mT and 50 Hz for 30 min/day/rat. The biomarkers were determined by spectrophotometry. The muscles (5/8) were stained with Hematoxylin-Eosin and examined by optic microscopy. Quantitative variables were statistically analyzed by the Fisher test, and categorical applying Pearson's Chi Squared test at p < 0.05 for all cases.In Groups B and C, the biomarkers were significantly increased compared to A, D, and E groups: fibrinogen (p < 0.001); NO, L-citrulline and carbonyl groups (p < 0.05); SOD (p < 0.01) as well as the percentage of area with inflammatory infiltration (p < 0.001).PEMF caused decreased levels of fibrinogen, L-citrulline, NO, SOD, and carbonyl groups and significant muscle recovery in rats with experimental myopathies.

Cardioprotective Effect of Ethanolic Extract of Cassia siamea Lamk. Leaves on Doxorubicin Induced Cardiac Toxicity in Rats

The present study was undertaken to assess the cardioprotective effect of ethanolic extract of Cassia siamea Lamk. leaves on Doxorubicin induced cardiac myopathy in rats. Doxorubicin was administered to rats in six equal doses intraperitoneally over a period of two weeks (cumulative dose of 15 mg/Kg) for all the study groups except normal group. The pretreatment for one week with ethanolic extract of C. siamea Lamk. leaves was given to the respective groups to assess the cardioprotective activity. On the 22 nd day various parameters such as body weight, heart weight, heart/body weight ratio, ECG recording, Invasive BP determination, serum markers such as creatine kinase - MB (CK - MB), lactatedehydrogenase (LDH), SGOT and SGPT was estimated. The tissue antioxidant markers viz. catalase (CAT), superoxide dismutase (SOD) and extent of lipid peroxidation viz. malondialdehyde (MDA) was also estimated. The Histopathological study of heart was carried out to assess the cardioprotective activity of the extract on Doxorubicin induced cardiac toxicity. Doxorubicin cause increase in all the serum enzyme markers and also alters the normal ECG pattern and blood pressure, while the ethanolic extract of C. siamea Lamk. (EECS) leaves significantly reduced the elevated levels of the enzymes and restores the ECG and BP close to normal. The EECS also significantly increased the tissue antioxidant levels of CAT and SOD, while decrease the MDA level and also restores the Histopathological architecture of the heart near to normal when compared with the groups treated with Doxorubicin control.

Biomarkers of Drug-Induced Skeletal Muscle Injury in the Rat: Troponin I and Myoglobin

The purpose of this investigation was to determine the utility of fast-twitch skeletal muscle troponin I (fsTnI) and urinary myoglobin (uMB) as biomarkers of skeletal muscle injury in 8-week-old Sprague-Dawley rats. fsTnI and uMB were quantified by enzyme-linked immunosorbent assay and compared with standard clinical assays including creatine kinase, aldolase, aspartate aminotransferase, and histopathological assessments. Detectable levels of uMB were normalized to urinary creatinine to control for differences in renal function. Seven compounds, including those with toxic effects on skeletal muscle, cardiac muscle, or liver, were evaluated. fsTnI was typically nondetectable (< 5.9 ng/ml serum) in vehicle-treated female and male rats but increased in a dose-dependent manner to at least 300 ng/ml in cerivastatin-induced severe fast-twitch specific myotoxicity. Minimal myopathy induced by investigational compounds BMS-600149 and BMS-687453 increased serum fsTnI to about 30-50 ng/ml, suggesting a reasonable dynamic range for detecting mild to severe skeletal muscle toxicity. In direct contrast, fsTnI was only marginally increased relative to population control values in rats treated with triamcinolone acetonide, which produces muscle atrophy or the cardiotoxins isoproterenol and CoCl2. uMB was typically nondetectable (< 1.6 ng/ml urine) in vehicle-treated female and male rats but increased to approximately 140, 300, and 30 ng/mg creatinine in rats treated with cerivastatin, BMS-687453, and triamcinolone acetonide, respectively. Cardiotoxicity also increased uMB in rats treated with isoproterenol and CoCl2 with urine concentrations ranging from 20 to 30 ng/mg creatinine. Severe hepatotoxicity (coumarin) did not significantly affect serum fsTnI or uMB levels. Collectively, these data suggest that fsTnI is specific for skeletal muscle toxicity, whereas uMB is nonspecific, increasing with skeletal muscle and cardiac toxicity. Accordingly, the complement of fsTnI and uMB, in conjunction with standard clinical assays may comprise a useful diagnostic panel for assessing drug-induced myopathy in rats.

Oxidant-induced atrogin-1 and transforming growth factor-beta1 precede alcohol-related myopathy in rats.

Alcohol-related chronic myopathy is characterized by severe biochemical and structural changes to skeletal muscle. Our goals were to: (1) identify early regulatory elements that precede the overt manifestation of plantaris atrophy; and (2) circumvent these derangements by supplementing alcohol-fed rats with the glutathione precursor, procysteine. After 6 weeks of daily ingestion, before the development of overt atrophy of the plantaris muscle, alcohol increased several markers of oxidative stress and increased gene expressions of atrogin-1 and transforming growth factor-beta1 (TGF-beta1) by approximately 60- and approximately 65-fold, respectively, which were attenuated by procysteine supplementation. Interestingly, after 28 weeks of alcohol ingestion, when overt plantaris atrophy had developed, atrogin-1 and TGF-beta1 gene expression had returned to baseline levels. Together, these findings suggest that alcohol-induced, redox-sensitive alterations drive pro-atrophy signaling pathways that precede muscle atrophy. Therefore, targeted anti-oxidant treatments such as procysteine supplementation may benefit individuals with chronic alcohol abuse, particularly if given prior to the development of clinically significant myopathy.